Methods for treating airways

ABSTRACT

This relates to treating airways in a lung to decrease asthmatic symptoms. The also includes steps of measuring a parameter of an airway at a plurality of locations in a lung, identifying at least one treatment site from at least one of the plurality of locations based on the parameter, and applying energy to the treatment site to reduce the ability of the site to narrow.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/171,973, filed Feb. 4, 2014, which is a continuation of U.S. patentapplication Ser. No. 13/557,518, filed Jul. 25, 2012, now abandoned,which is a continuation of U.S. patent application Ser. No. 11/398,353,filed Apr. 4, 2006, now U.S. Pat. No. 8,251,070, the entireties of eachof which are incorporated herein by reference. This application isrelated to U.S. patent application Ser. No. 10/640,967, filed Aug. 13,2003, and U.S. patent application Ser. No. 09/535,856, filed Mar. 27,2000, the entireties of each of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION

The invention relates to a method of treating a lung having at least onesymptom of reversible obstructive pulmonary disease, and moreparticularly, methods of treating airways in a lung to decreaseasthmatic symptoms of the lung, by measuring a parameter of an airway ata plurality of locations in a lung, identifying at least one treatmentsite from at least one of the plurality of locations based on theparameter; and applying energy to the treatment site to reduce theability of the site to narrow.

Reversible obstructive pulmonary disease includes asthma and reversibleaspects of chronic obstructive pulmonary disease (COPD). Asthma is adisease in which (i) bronchoconstriction, (ii) excessive mucusproduction, and (iii) inflammation and swelling of airways occur,causing widespread but variable airflow obstruction thereby making itdifficult for the asthma sufferer to breathe. Asthma is furthercharacterized by acute episodes of airway narrowing via contraction ofhyper-responsive airway smooth muscle.

The reversible aspects of COPD include excessive mucus production andpartial airway occlusion, airway narrowing secondary to smooth musclecontraction, and bronchial wall edema and inflation of the airways.Usually, there is a general increase in bulk (hypertrophy) of the largebronchi and chronic inflammatory changes in the small airways. Excessiveamounts of mucus are found in the airways and semisolid plugs of mucusmay occlude some small bronchi. Also, the small airways are narrowed andshow inflammatory changes.

In asthma, chronic inflammatory processes in the airway play a centralrole in increasing the resistance to airflow within the lungs. Manycells and cellular elements are involved in the inflammatory process,particularly mast cells, eosinophils T lymphocytes, neutrophils,epithelial cells, and even airway smooth muscle itself. The reactions ofthese cells result in an associated increase in sensitivity andhyper-responsiveness of the airway smooth muscle cells lining theairways to particular stimuli.

The chronic nature of asthma can also lead to remodeling of the airwaywall (i.e., structural changes such as airway wall thickening or chronicedema) that can further affect the function of the airway wall andinfluence airway hyper-responsiveness. Epithelial denudation exposes theunderlying tissue to substances that would not normally otherwisecontact the underlying tissue, further reinforcing the cycle of cellulardamage and inflammatory response.

In susceptible individuals, asthma symptoms include recurrent episodesof shortness of breath (dyspnea), wheezing, chest tightness, and cough.Currently, asthma is managed by a combination of stimulus avoidance andpharmacology.

Stimulus avoidance is accomplished via systematic identification andminimization of contact with each type of stimuli. It may, however, beimpractical and not always helpful to avoid all potential stimuli.

Asthma is managed pharmacologically by: (1) long term control throughuse of anti-inflammatories and long-acting bronchodilators and (2) shortterm management of acute exacerbations through use of short-actingbronchodilators. Both of these approaches require repeated and regularuse of the prescribed drugs. High doses of corticosteroidanti-inflammatory drugs can have serious side effects that requirecareful management. In addition, some patients are resistant to steroidtreatment. The difficulty involved in patient compliance withpharmacologic management and the difficulty of avoiding stimulus thattriggers asthma are common barriers to successful asthma management.

Asthma is a serious disease with growing numbers of sufferers. Currentmanagement techniques are neither completely successful nor free fromside effects.

Accordingly, it would be desirable to provide an asthma treatment whichimproves airflow without the need for patient compliance.

In addition to the airways of the lungs, other body conduits such as theesophagus, ureter, urethra, and coronary arteries, are also subject toinflammation and periodic reversible spasms that produce obstruction toflow.

SUMMARY OF THE INVENTION

The present invention relates to methods for treating a lung, preferablyhaving at least one symptom of reversible obstructive pulmonary disease,comprising the steps of advancing a treatment device into the lung andtreating the lung with the device to at least reduce the ability of thelung to produce at least one symptom of reversible obstructive pulmonarydisease and to decrease the resistance to the flow of air through thelung.

A variation of the invention includes the method described above furthercomprising the step of locating one or more treatment sites within anairway of the lung, selecting at least one of the treatment sites andtreating at least one of the treatment sites selected in the selectingstep. The invention may further include performing the steps while thelung is experiencing at least one symptom of either natural orartificially induced reversible obstructive pulmonary disease.

A further variation of the invention includes the method described aboveand further includes the steps of testing the lung for at least onepre-treatment pulmonary function value prior to the treating step, andre-testing the lung for at least one post-treatment pulmonary functionvalue subsequent to the treating step.

A further variation of the invention includes the method described abovefurther comprising identifying treatment sites within the airway beinghighly susceptible to either airway inflammation, airway constriction,excessive mucus secretion, or any other symptom of reversibleobstructive pulmonary disease.

Another variation of the invention includes the method described aboveand the additional step of stimulating the lung to produce at least oneartificially induced symptom of reversible obstructive pulmonarydisease. The invention may further comprise the step of evaluating theresults of the stimulating step.

Another variation of the invention includes the method described abovewhere treating at least airway tissue within the lung further comprisesthe step of determining the effect of the treatment by visuallyobserving the airway for blanching, or a change in appearance, of airwaytissue.

Another variation of the invention includes the method described abovewhere treating at least airway tissue at a treatment site within thelung further comprises the step of monitoring electrical impedance oftissue at one or more points.

Another variation of the invention includes the method described abovewhere treating the lung includes sub-mucosal treatment of at leastairway tissue in the lung.

Another variation of the invention includes the method described abovewhere the treating step includes treating the lung by depositing aradioactive substance in at least one treatment site within the lung.

Another variation of the invention include the method described abovefurther including the step of scraping tissue from a wall of an airwaywithin the lung prior to the treating step. The invention may furthercomprise depositing a substance on the scraped wall of the airway.

Another variation of the invention includes the method described abovewhere the treating step uses a modality selected from the groupconsisting of mechanical, chemical, radio frequency, radioactive energy,heat, and ultrasound.

Another variation of the invention includes the method described abovefurther comprising pre-treating the lung to at least reduce the abilityof the lung to produce at least one symptom of reversible obstructivepulmonary disease prior to the treating step, where at least oneparameter of the pre-treating step is lesser than at least one parameterof the treating step.

Another variation of the invention comprises the method described abovewhere the treating step includes separating the treating step intostages to reduce the healing load on the lung. The separating step maycomprise treating different regions of the lung at different times ordividing the number of treatment sites into a plurality of groups oftreatment sites and treating each group at a different time.

Another variation of the invention includes the method described abovefurther comprising sensing movement of the lung and repositioning thetreatment device in response to said sensing step.

Another variation of the invention includes the method described abovefurther comprising reducing the temperature of lung tissue adjacent to atreatment site.

Another variation of the invention includes the method described abovefurther comprising the step of providing drug therapy, exercise therapy,respiratory therapy, and/or education on disease management techniquesto further reduce the effects of reversible obstructive pulmonarydisease.

The invention further includes the method for reversing a treatment toreduce the ability of the lung to produce at least one symptom ofreversible obstructive pulmonary disease comprising the step ofstimulating re-growth of smooth muscle tissue in the lung.

The invention further includes the method of evaluating an individualhaving reversible obstructive pulmonary disease as a candidate for aprocedure to reduce the ability of the individual's lung to produce atleast one reversible obstructive pulmonary disease symptom by treatingan airway within the lung of the individual, the method comprising thesteps of assessing the pulmonary condition of the individual, comparingthe pulmonary condition to a corresponding predetermined state; andevaluating the individual based upon the comparing step. The method mayadditionally comprise the steps of performing pulmonary function testson the individual to obtain at least one pulmonary function value,comparing the at least one pulmonary function value to a correspondingpredetermined pulmonary function value, and evaluating the individualbased upon the comparing step.

The invention further comprises a method of evaluating the effectivenessof a procedure to reduce the ability of lung to produce at least onesymptom of reversible obstructive pulmonary disease previously performedon an individual having reversible obstructive pulmonary disease, themethod comprising the steps of assessing the pulmonary condition of theindividual, comparing the pulmonary condition to a correspondingpredetermined state; and evaluating the effectiveness of the procedurebased upon the comparing step. The method may additionally comprise thesteps of performing pulmonary function tests on the individual to obtainat least one pulmonary function value, treating the lung to at leastreduce the ability of the lung to produce at least one symptom ofreversible obstructive pulmonary disease, performing post-procedurepulmonary function tests on the individual to obtain at least onepost-procedure pulmonary function value; and comparing the pulmonaryfunction value with the post-procedure pulmonary function value todetermine the effect of the treating step.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in greater detail with reference tothe various embodiments illustrated in the accompanying drawings:

FIG. 1 is a cross sectional view of an airway in a healthy lung.

FIG. 2 shows a section through a bronchiole having an airway diametersmaller than that shown in FIG. 1.

FIG. 3 illustrates the airway of FIG. 1 in which the smooth muscle 14has hypertrophied and increased in thickness causing reduction of theairway diameter.

FIG. 4A is a schematic view of the lungs being treated with a treatmentdevice as described herein.

FIG. 4B illustrates one example of a treatment system for use with themethods described herein.

FIG. 4C illustrates another variation of a treatment system that appliesthe treatment externally to the lungs.

FIG. 5 illustrates a map to aid in treatment of the airways.

FIG. 6A illustrates a device that stimulates the airway intocontracting.

FIGS. 6B-6F illustrate various modes of measuring parameters within thelungs to identify treatment sites.

FIG. 7 is a side view of a device extending out of anendoscope/bronchoscope, where the device has an active distal end fortreating tissue using energy delivery.

FIG. 8 shows various features of a device allowing for low forcedeployment of an energy element.

DETAILED DESCRIPTION

The invention relates to methods for improving airflow through theairways of a lung having reversible obstructive pulmonary disease. It isintended that the invention is applicable to any aspect of reversibleobstructive pulmonary disease, including but not limited to asthma. Oneway of improving airflow is to decrease the resistance to airflow withinthe lungs. There are several approaches to reducing this resistance,including but not limited to reducing the ability of the airway tocontract, increasing the airway diameter, reducing the inflammation ofairway tissues, and/or reducing the amount of mucus plugging of theairway. Another approach to reducing resistance is to increase theresting airway diameter of an airway such that any subsequent narrowingwill not reduce the airway to a diameter such that obstruction toairflow is discernable by the patient. The present invention includesadvancing a treatment device into the lung and treating the lung to atleast reduce the ability of the lung to produce at least one symptom ofreversible obstructive pulmonary disease. The following is a briefdiscussion of some causes of increased resistance to airflow within thelungs and the inventive treatment of the invention described herein. Assuch, the following discussion is not intended to limit the aspects orobjective of the inventive method as the inventive method may causephysiological changes not described below but such changes stillcontributing to reducing or eliminating at least one of the symptoms ofreversible obstructive pulmonary disease.

Reducing the Ability of the Airway to Contract

The inventive treatment reduces the ability of the airways to narrow orto reduce in diameter due to airway smooth muscle contraction. Theinventive treatment uses a modality of treatments including, but notlimited to the following: chemical, radio frequency, radioactivity,heat, ultrasound, radiant, laser, microwave, or mechanical energy (suchas in the form of cutting, punching, abrading, rubbing, or dilating).This treatment reduces the ability of the smooth muscle to contractthereby lessening the severity of an asthma attack. The reduction in theability of the smooth muscle to contract may be achieved by treating thesmooth muscle itself or by treating other tissues which in turninfluence smooth muscle contraction or the response of the airway to thesmooth muscle contraction. Treatment may also reduce airwayresponsiveness or the tendency of the airway to narrow or to constrictin response to a stimulus.

The amount of smooth muscle surrounding the airway can be reduced byexposing the smooth muscle to energy which either kills the muscle cellsor prevents these cells from replicating. The reduction in smooth musclereduces the ability of the smooth muscle to contract and to narrow theairway during a spasm. The reduction in smooth muscle and surroundingtissue has the added potential benefit of increasing the caliber ordiameter of the airways, which further reduces the resistance to airflowthrough the airways. In addition to the use of debulking smooth muscletissue to open up the airways, the device used in the present inventionmay also eliminate smooth muscle altogether by damaging or destroyingthe muscle. The elimination of the smooth muscle prevents thecontraction or spasms of hyper-reactive airways of a patient havingreversible obstructive pulmonary disease. By doing so, the eliminationof the smooth muscle may reduce some symptoms of reversible obstructivepulmonary disease.

The ability of the airway to contract can also be altered by treatmentof the smooth muscle in particular patterns. The smooth muscle isarranged around the airways in a generally helical pattern with pitchangles ranging from about −38 to about +38 degrees. Thus, the treatmentof the smooth muscle in appropriate patterns interrupts or cuts throughthe helical pattern of the smooth muscle at a proper pitch and preventsthe airway from constricting. This procedure of patterned treatmentapplication eliminates contraction of the airways without completelyeradicating smooth muscle and other airway tissue. A pattern fortreatment may be chosen from a variety of patterns includinglongitudinal or axial stripes, circumferential bands, helical stripes,and the like as well as spot patterns having rectangular, elliptical,circular or other shapes. The size, number, and spacing of the treatmentbands, stripes, or spots are chosen to provide a desired clinical effectof reduced airway responsiveness while limiting insult to the airway toa clinically acceptable level.

The patterned treatment of the tissues surrounding the airways withenergy provides various advantages. The careful selection of the portionof the airway to be treated allows desired results to be achieved whilereducing the total healing load. Patterned treatment can also achievedesired results with decreased morbidity, preservation of epithelium,and preservation of a continuous or near continuous ciliated innersurface of the airway for mucociliary clearance. The pattern oftreatment may also be chosen to achieve desired results while limitingtotal treatment area and/or the number of airways treated, therebyimproving speed and ease of treatment.

Application of energy to the tissue surrounding the airways may alsocause the DNA of the cells to become cross linked. The treated cellswith cross linked DNA are incapable of replicating. Accordingly, overtime, as the smooth muscle cells die, the total thickness of smoothmuscle decreases because of the inability of the cells to replicate. Theprogrammed cell death causing a reduction in the volume of tissue iscalled apoptosis. This treatment does not cause an immediate effect butcauses shrinking of the smooth muscle and opening of the airway overtime and substantially prevents re-growth. The application of energy tothe walls of the airway may also be used to cause a cross linking of theDNA of the mucus gland cells thereby preventing them from replicatingand reducing excess mucus plugging or production over time.

The ability of the airways to contract may also be reduced by alteringmechanical properties of the airway wall, such as by increasingstiffness of the wall or by increasing parenchymal tethering of theairway wall. Both of these methods increase the strength of the airwaywall and further oppose contraction and narrowing of the airway.

There are several ways to increase the stiffness of the airway wall. Oneway to increase stiffness is to induce fibrosis or a wound healingresponse by causing trauma to the airway wall. The trauma can be causedby delivery of therapeutic energy to the tissue in the airway wall, bymechanical insult to the tissue, or by chemically affecting the tissue.The energy is preferably delivered in such a way that it minimizes orlimits the intra-luminal thickening that may occur.

Another way to increase the effective stiffness of the airway wall is toalter the submucosal folding of the airway upon narrowing. The mucosallayer includes the epithelium, its basement membrane, and the laminapropria, a subepithelial collagen layer. The submucosal layer may alsoplay a role in airway folding. As an airway narrows, its perimeterremains relatively constant, with the mucosal layer folding upon itself.As the airway narrows further, the mucosal folds mechanically interferewith each other, effectively stiffening the airway. In asthmaticpatients, the number of folds is fewer and the size of the folds islarger, and thus, the airway is free to narrow with less mechanicalinterference of mucosal folds than in a healthy patient. Thus, asthmaticpatients have a decrease in airway stiffness and the airways have lessresistance to narrowing.

The mucosal folding in asthmatic patients can be improved by treatmentof the airway in a manner which encourages folding. Preferably, atreatment will increase the number of folds and/or decrease the size ofthe folds in the mucosal layer. For example, treatment of the airwaywall in a pattern such as longitudinal stripes can encourage greaternumber of smaller mucosal folds and increase airway stiffness.

The mucosal folding can also be increased by encouraging a greaternumber of smaller folds by reducing the thickness of the mucosa and/orsubmucosal layer. The decreased thickness of the mucosa or submucosa maybe achieved by application of energy which either reduces the number ofcells in the mucosa or submucosal layer or which prevents replication ofthe cells in the mucosa or submucosal layer. A thinner mucosa orsubmucosal layer will have an increased tendency to fold and increasedmechanical stiffening caused by the folds.

Another way to reduce the ability of the airways to contract is toimprove parenchymal tethering. The parenchyma surrounds airways andincludes the alveolus and tissue connected to and surrounding the outerportion of the airway wall. The parenchyma includes the alveolus andtissue connected to and surrounding the cartilage that supports thelarger airways. In a healthy patient, the parenchyma provides a tissuenetwork which connects to and helps to support the airway. Edema oraccumulation of fluid in lung tissue in patients with asthma or COPD isbelieved to decouple the airway from the parenchyma reducing therestraining force of the parenchyma which opposes airway constriction.Energy can be used to treat the parenchyma to reduce edema and/orimprove parenchymal tethering.

In addition, the applied energy may be used to improve connectionbetween the airway smooth muscle and submucosal layer to the surroundingcartilage, and to encourage wound healing, collagen deposition, and/orfibrosis in the tissue surrounding the airway to help support the airwayand prevent airway contraction.

Increasing the Airway Diameter

Hypertrophy of smooth muscle, chronic inflammation of airway tissues,and general thickening of all parts of the airway wall can reduce theairway diameter in patients with reversible obstructive pulmonarydisease. Increasing the overall airway diameter using a variety oftechniques can improve the passage of air through the airways.Application of energy to the airway smooth muscle of an asthmaticpatient can debulk or reduce the volume of smooth muscle. This reducedvolume of smooth muscle increases the airway diameter for improved airexchange.

Reducing inflammation and edema of the tissue surrounding the airway canalso increase the diameter of an airway. Inflammation and edema(accumulation of fluid) of the airway are chronic features of asthma.The inflammation and edema can be reduced by application of energy tostimulate wound healing and regenerate normal tissue. Healing of theepithelium or sections of the epithelium experiencing ongoing denudationand renewal allows regeneration of healthy epithelium with lessassociated airway inflammation. The less inflamed airway has anincreased airway diameter both at a resting state and in constriction.The wound healing can also deposit collagen which improves parenchymaltethering.

Inflammatory mediators released by tissue in the airway wall may serveas a stimulus for airway smooth muscle contraction. Therapy that reducesthe production and release of inflammatory mediator can reduce smoothmuscle contraction, inflammation of the airways, and edema. Examples ofinflammatory mediators are cytokines, chemokines, and histamine. Thetissues which produce and release inflammatory mediators include airwaysmooth muscle, epithelium, and mast cells. Treatment of these structureswith energy can reduce the ability of the airway structures to produceor release inflammatory mediators. The reduction in releasedinflammatory mediators will reduce chronic inflammation, therebyincreasing the airway inner diameter, and may also reducehyper-responsiveness of the airway smooth muscle.

A further process for increasing the airway diameter is by denervation.A resting tone of smooth muscle is nerve regulated by release ofcatecholamines. Thus, by damaging or eliminating nerve tissue in theairways the resting tone of the smooth muscle is reduced, and the airwaydiameter is increased. Resting tone may also be reduced by directlyaffecting the ability of smooth muscle tissue to contract.

Reducing Plugging of the Airway

Excess mucus production and mucus plugging are common problems duringboth acute asthma exacerbation and in chronic asthma management. Excessmucus in the airways increases the resistance to airflow through theairways by physically blocking all or part of the airway. Excess mucusmay also contribute to increased numbers of leukocytes found in airwaysof asthmatic patients by trapping leukocytes. Thus, excess mucus canincrease chronic inflammation of the airways.

One type of asthma therapy involves treatment of the airways with energyto target and reduce the amount of mucus producing cells, ducts, andglands and to reduce the effectiveness of the remaining mucus producingcells and glands. The treatment can eliminate all or a portion of themucus producing cells, ducts, and glands, can prevent the cells fromreplicating or can inhibit their ability to secrete mucus. Thistreatment will have both chronic benefits in increasing airflow throughthe airways and will lessen the severity of acute exacerbation of thesymptoms of reversible obstructive pulmonary disease.

Application of Treatment

The following illustrations are examples of the invention describedherein. It is contemplated that combinations of aspects of specificembodiments or combinations of the specific embodiments themselves arewithin the scope of this disclosure.

FIGS. 1 and 2 illustrate cross sections of two different airways in ahealthy patient. The airway of FIG. 1 is a medium sized bronchus havingan airway diameter D1 of about 3 mm. FIG. 2 shows a section through abronchiole having an airway diameter D2 of about 1.5 mm. Each airwayincludes a folded inner surface or epithelium 10 surrounded by stroma 12and smooth muscle tissue 14. The larger airways including the bronchusshown in FIG. 1 also have mucous glands 16 and cartilage 18 surroundingthe smooth muscle tissue 14. Nerve fibers 20 and blood vessels 24 alsosurround the airway.

FIG. 3 illustrates the bronchus of FIG. 1 in which the smooth muscle 14has hypertrophied and increased in thickness causing the airway diameterto be reduced from the diameter D1 to a diameter D3.

FIG. 4A is a schematic side view of the lungs being treated with atreatment device 38 according to the present invention. The treatmentdevice 100 is an elongated member for treating tissue at a treatmentsite 34 within a lung. Although the invention discusses treatment oftissue at the airway wall surface it is also intended that the inventioninclude treatment below an epithelial layer of the lung tissue. Theinvention may also rely on the use of an imaging device 36 to enable theidentification of at least one treatments site from the plurality ofpossible treatment site locations. The imaging device may employradiographic visualization such as fluoroscopy or other externalvisualization means such as computer aided tomography (CT), magneticresonance imaging (MRI), positron emission tomography (PET), opticalcoherence tomography, or ultrasonic imaging. The imaging device may beexternal as shown. Alternatively, the imaging device may have acomponent that is affixed to the treatment system 32 or otherwise isinserted in to the body.

FIG. 4B represents one example of a treatment system 32 according to thepresent invention. In this variation, the system 32 delivers therapeuticenergy to tissue of a patient via a device 100. Variations of devicesare described in U.S. application Ser. Nos. 11/255,796 and 11/256,295both filed Oct. 21, 2005 and the entirety of each of which isincorporated by reference.

FIG. 4B shows a schematic diagram of one example of a system 32 fordelivering therapeutic energy to tissue of a patient for use with thedevice described herein. The illustrated variation shows, the system 32having a power supply (e.g., consisting of an energy generator 112, acontroller 114 coupled to the energy generator, a user interface surface116 in communication with the controller 114). It is noted that thedevice may be used with a variety of systems (having the same ordifferent components). For example, although variations of the deviceshall be described as RF energy delivery devices, variations of thedevice may include resistive heating systems, infrared heating elements,microwave energy systems, focused ultrasound, cryo-ablation, or anyother energy deliver system. It is noted that the devices describedshould have sufficient length to access the tissue targeted fortreatment. For example, it is presently believed necessary to treatairways as small as 3 mm in diameter to treat enough airways for thepatient to benefit from the described treatment (however, it is notedthat the invention is not limited to any particular size of airways andairways smaller than 3 mm may be treated). Accordingly, devices fortreating the lungs must be sufficiently long to reach deep enough intothe lungs to treat these airways. Accordingly, the length of thesheath/shaft of the device that is designed for use in the lungs shouldpreferably be between 1.5-3 ft long in order to reach the targetedairways.

The particular system 32 depicted in FIG. 4B is one having a userinterface as well as safety algorithms that are useful for the asthmatreatment discussed above. Addition information on such a system may befound in U.S. Provisional application Nos. 60/674,106, and 60/673,876both filed Apr. 21, 2005 the entirety of each of which is incorporatedby reference herein.

Referring again to FIG. 4B, a variation of a device 100 described hereinincludes a flexible sheath 202, an elongate shaft 204 (in this example,the shaft extends out from the distal end of the sheath 202), and ahandle or other operator interface 206 (optional) secured to a proximalend of the sheath 202. The distal portion of the device 100 includes anenergy transfer element 208 (e.g., an electrode, a basket electrode, aresistive heating element, cryoprobe, etc.). Additionally, the deviceincludes a connector 210 common to such energy delivery devices. Theconnector 210 may be integral to the end of a cable 212 as shown, or theconnector 210 may be fitted to receive a separate cable 212. In anycase, the device is configured for attachment to the power supply viasome type connector 210. The elongate portions of the device 202 and 204may also be configured and sized to permit passage through the workinglumen of a commercially available bronchoscope or endoscope. Asdiscussed herein, the device is often used within an endoscope,bronchoscope or similar device. However, the device may also be advancedinto the body with or without a steerable catheter, in a minimallyinvasive procedure or in an open surgical procedure, and with or withoutthe guidance of various vision or imaging systems.

FIG. 4B also illustrates additional components used in variations of thesystem. Although the depicted systems are shown as RF type energydelivery systems, it is noted that the invention is not limited as such.Other energy delivery configurations contemplated may include or notrequire some of the elements described below. The power supply (usuallythe user interface portion 116) shall have connections 120, 128, 130 forthe device 100, return electrode 124 (if the system 32 employs amonopolor RF configuration), and actuation pedal(s) 126 (optional). Thepower supply and controller may also be configured to deliver RF energyto an energy transfer element configured for bipolar RF energy delivery.The user interface 116 may also include visual prompts 132, 160, 168,174 for user feedback regarding setup or operation of the system. Theuser interface 116 may also employ graphical representations ofcomponents of the system, audio tone generators, as well as otherfeatures to assist the user with system use.

In many variations of the system, the controller 114 includes aprocessor 122 that is generally configured to accept information fromthe system and system components, and process the information accordingto various algorithms to produce control signals for controlling theenergy generator 112. The processor 122 may also accept information fromthe system 110 and system components, process the information accordingto various algorithms and produce information signals that may bedirected to the visual indicators, digital display or audio tonegenerator of the user interface in order to inform the user of thesystem status, component status, procedure status or any other usefulinformation that is being monitored by the system. The processor 122 ofthe controller 114 may be digital IC processor, analog processor or anyother suitable logic or control system that carries out the controlalgorithms.

In one variation of the system shown in FIG. 4B, the RF generator 112generates RF energy at a frequency of about 400 kHz to about 500 kHz inwith a wattage output sufficient to maintain a target tissue temperatureof about 60 degrees C. to about 80 degrees C., specifically, about 60degrees C. to about 70 degrees C. (when measuring at a surface of theelectrode). The duration of the activation state for an embodiment of asingle treatment cycle may be about 1 seconds to about 15 seconds,specifically, about 8 seconds to about 12 seconds. Alternatively, theduration of the activation state of the RF generator may also be set tonot more than the duration required to deliver about 150 Joules ofenergy to the target tissue, specifically, not more than the durationrequired to deliver about 125 Joules of RF energy to target tissue.

Additional examples of devices for use with the methods of thisinvention are found in the following U.S. patent application Ser. Nos.09/095,323 and 09/436,455; U.S. Pat. Nos. 6,488,673 and 6,411,852. Theentirety of each of the aforementioned applications is incorporated byreference herein.

FIG. 4C represents another schematic side view of lungs being treatedwith a treatment device 100 according to the present invention. In thisvariation, the treatment device 100 and system 32 are external to thelungs and/or body but still applies energy to within the lungs. Forexample, such a treatment may use a high frequency ultrasound (commonlyreferred to as HIFU). As discussed above, the invention may also rely onthe use of an imaging device 36.

The treatment of an airway with the treatment device may involve placinga visualization system such as an endoscope or bronchoscope into theairways. The treatment device is then inserted through or next to thebronchoscope or endoscope while visualizing the airways. Alternatively,the visualization system may be built directly into the treatment deviceusing fiber optic imaging and lenses or a CCD and lens arranged at thedistal portion of the treatment device. The treatment device may also bepositioned using radiographic visualization such as fluoroscopy or otherexternal visualization means. The treatment device which has beenpositioned with a distal end within an airway to be treated is energizedso that energy is applied to the tissue of the airway walls in a desiredpattern and intensity. The distal end of the treatment device may bemoved through the airway in a uniform painting like motion to expose theentire length of an airway to be treated to the energy. The treatmentdevice may be passed axially along the airway one or more times toachieve adequate treatment. The “painting-like” motion used to exposethe entire length of an airway to the energy may be performed by movingthe entire treatment device from the proximal end either manually or bymotor. Alternatively, segments, stripes, rings or other treatmentpatterns may be used.

According to one variation of the invention, the energy is transferredto or from an airway wall in the opening region of the airway,preferably within a length of approximately two times the airwaydiameter or less, and to wall regions of airways distal to bifurcationsand side branches, preferably within a distance of approximately twicethe airway diameter or less. The invention may also be used to treatlong segments of un-bifurcated airway.

The invention includes a method of advancing a treatment device into alung and treating the lung with the device to, at least, reduce theability of the lung to produce at least one symptom of reversibleobstructive pulmonary disease. It is contemplated that the treatment mayreduce all of the symptoms of reversible obstructive disease.Alternatively, the treatment may be selected to address specificsymptoms of the disease. It is also intended that the treatment of thelung may sufficiently reduce the symptoms of reversible obstructivepulmonary disease such that the patient is able to function as thosefree from the disease. Alternatively, the treatment may be such that thesymptoms are reduced to allow the patient to more easily manage thedisease. It is also intended that the effects of the treatment may beeither long term or short term with repeating treatment necessary tosuppress the symptoms.

The methods of the invention described herein may be performed while thelung is experiencing natural symptoms of reversible obstructivepulmonary disease. One such example is where an individual, experiencingan asthma attack, or acute exacerbation of asthma or COPD, undergoestreatment to improve the individual's ability to breath. In such a case,the treatment, called ‘rescue,’ seeks to provide immediate relief forthe patient.

The method may also include the steps of locating one or more treatmentsites within an airway of the lung, selecting one of the treatment sitesfrom the locating step and treating at least one of the selectedtreatment sites. As mentioned above, these steps may be, but are notnecessarily, performed while the lung is experiencing symptoms ofreversible obstructive pulmonary disease.

The invention may further comprise the step of stimulating the lung toproduce at least one artificially induced symptom of reversibleobstructive pulmonary disease. For example, stimulation of the lungwould preferably increase the resistance to airflow within the lung,constrict airways within the lung, inflame/irritate airway tissues,increase edema and/or increase the amount of mucus plugging of theairway. Stimulation of the lung may occur at any point during theprocedure or before the procedure. For example, the lung may bestimulated either prior to or after, the step of locating a treatmentsite. If the lung is stimulated prior to the step of locating atreatment site, the reaction of the stimulated tissue within the lungmay be useful in determining which locations are to be selected astreatment sites. The lung tissue or airway tissue within the lung may bestimulated by a variety of methods including but not limited topharmacological stimulation, (e.g., histamine, methacholine, or otherbronchoconstricting agents, etc.), electrical stimulation, mechanicalstimulation, or any other stimuli causing obstructive pulmonarysymptoms. For example, electrical stimulation may comprise exposingairway tissue to electrical field stimulation. An example of suchparameters include 15 VDC, 0.5 ms pulses, 0.5-16 Hz, and 70 VDC, 2-3 mspulses, 20 HZ.

The locating step described above may be performed using a non-invasiveimaging technique, including but not limited to, a bronchogram, magneticresonance imaging, computed tomography, radiography (e.g., x-ray), andventilation perfusion scans.

The invention further includes the steps of testing the lung for atleast one pre-treatment pulmonary function value prior to treating thelung with the device. After the lung is treated, the lung is re-testedfor at least one post-treatment pulmonary function value. Naturally, thetwo pulmonary function values may be compared to estimate the effect ofthe treatment. The invention may also include treating additional sitesin the lung after the re-testing step to at least reduce the effect ofat least one symptom of reversible obstructive pulmonary disease. Theinvention may also include stimulating the lung to produce at least oneartificially induced symptom of reversible obstructive pulmonarydisease. As mentioned above, the stimulation of the lung may occur atany point during, or prior to, the procedure. For example, stimulationof the lung may occur prior to the step of testing the lung forpre-treatment pulmonary values. In this case, the values would bedeterminative of pulmonary function values of a lung experiencingsymptoms of reversible obstructive pulmonary disease. Accordingly, theobjective is to treat the lung until acceptable pulmonary functionvalues are obtained. One benefit of such a procedure is that the effectof the treatment on the patient is more readily observed as compared tothe situation where a patient, having previously been treated, must waitfor an attack of reversible obstructive pulmonary disease to determinethe efficacy of the treatment.

Pulmonary function values are well known in the art. The following is anexample of pulmonary function values that may be used. Other pulmonaryfunction values, or combinations thereof, are intended to be within thescope of this invention. The values include, but are not limited to, FEV(forced expiratory volume), FVC (forced vital capacity), FEF (forcedexpiratory flow), Vmax (maximum flow), PEFR (peak expiratory flow rate),FRC (functional residual capacity), RV (residual volume), TLC (totallung capacity).

FEV measures the volume of air exhaled over a pre-determined period oftime by a forced expiration immediately after a full inspiration. FVCmeasures the total volume of air exhaled immediately after a fullinspiration. Forced expiratory flow measures the volume of air exhaledduring a FVC divided by the time in seconds. Vmax is the maximum flowmeasured during FVC. PEFR measures the maximum flow rate during a forcedexhale starting from full inspiration. RV is the volume of air remainingin the lungs after a full expiration.

The locating step described above may also comprise identifyingtreatment sites within the airway being susceptible to a symptom ofreversible obstructive pulmonary disease. For example, symptoms mayinclude, but are not limited to, airway inflammation, airwayconstriction, excessive mucous secretion, or any other asthmaticsymptom. Stimulation of the lung to produce symptoms of reversibleobstructive pulmonary disease may assist in identifying ideal treatmentsites.

As noted above, the method of the present invention may includestimulating the lung to produce at least one artificially inducedsymptom of reversible obstructive pulmonary disease and further includethe step of evaluating the result of stimulation of the lung. Forexample, the evaluating step may include visually evaluating the effectof the stimulating step on the airway using a bronchoscope with avisualization system or by non-invasive imaging techniques, such asthose describe herein. The evaluating step may include measuringpressure changes in the airway before and after the stimulating step.Pressure may be measured globally (e.g., within the entire lung), orlocally (e.g., within a specific section of the lung such as an airwayor alveolar sac.) Also, the evaluating step may comprise measuring theelectrical properties of the tissue before and after the stimulatingstep. The invention may also include evaluating the results of thestimulating step by combining any of the methods previously mentioned.Also, the invention may further comprise the step of selecting at leastone treatment parameter based upon the results of the evaluating step.Such treatment parameters may include, but are not limited to, durationof treatment, intensity of treatment, temperature, amount of tissuetreated, depth of treatment, etc.

The method may also include the step of determining the effect of thetreatment by visually observing lung, airway or other such tissue forblanching of the tissue. The term “blanching” is intended to include anyphysical change in tissue that is usually, but not necessarily,accompanied by a change in the color of the tissue. One example of suchblanching is where the tissue turns to a whitish color after thetreatment of application of energy.

The invention may also include the step of monitoring impedance across atreated area of tissue within the lung. Measuring impedance may beperformed in cases of monopolar or bipolar energy delivery devices.Additionally, impedance may be monitored at more than one site withinthe lungs. The measuring of impedance may be, but is not necessarily,performed by the same electrodes used to deliver the energy treatment tothe tissue. Furthermore, the invention includes adjusting the treatmentparameters based upon the monitoring of the change in impedance afterthe treatment step. For example, as the energy treatment affects theproperties of the treated tissue, measuring changes in impedance mayprovide information useful in adjusting treatment parameters to obtain adesired result.

Another aspect of the invention includes advancing a treatment deviceinto the lung and treating lung tissue to at least reduce the ability ofthe lung to produce at least one symptom of reversible obstructivepulmonary disease and further comprising the step of sub-mucosal sensingof the treatment to the lung tissue. The sub-mucosal sensing may beinvasive such as when using a probe equipped to monitor temperature,impedance, and/or blood flow. Or, the sub-mucosal sensing may benon-invasive in such cases as infra-red sensing.

The invention may also include using the treatment device to depositradioactive substances at select treatment sites within the lung. Theradioactive substances, including, but not limited to Iridium (e.g.192Ir.) either treat the lung tissue over time or provide treatment uponbeing deposited.

The invention also includes scraping epithelial tissue from the wall ofan airway within the lung prior to advancing a treatment device into thelung to treat the lung tissue. The removal of the epithelial tissueallows the device to treat the walls of an airway more effectively. Theinvention further comprises the step of depositing a substance on thescraped wall of the airway after the device treats the airway wall. Thesubstance may include epithelial tissue, collagen, growth factors, orany other bio-compatible tissue or substance, which promotes healing,prevents infection, and/or assists in the clearing of mucus.Alternatively, the treatment may comprise the act of scraping epithelialtissue to induce yield the desired response.

The invention includes using the treating device to pre-treat the lungto at least reduce the ability of the lung to produce at least onesymptom of reversible obstructive pulmonary disease prior to thetreating step. At least one of the parameters of the pre-treating stepmay differ than one of the parameters of the treating step. Suchparameters may include time, temperature, amount of tissue over whichtreatment is applied, amount of energy applied, depth of treatment, etc.

The invention may also include advancing the treatment device into thelung and treating the lung tissue in separate stages. One of thebenefits of dividing the treating step into separate stages is that thehealing load of the patient is lessened. Dividing of the treating stepmay be accomplished by treating different regions of the lung atdifferent times. Or, the total number of treatment sites may be dividedinto a plurality of groups of treatment sites, where each group oftreatment sites is treated at a different time. The amount of timebetween treatments may be chosen such that the healing load placed onthe lungs is minimized.

The invention may also include advancing a treatment device into thelung, treating the lung with the device and sensing movement of the lungto reposition the treatment device in response to the movement. Thissensing step accounts for the tidal motion of the lung during breathingcycles or other movement. Taking into account the tidal motion allowsimproved accuracy in repositioning of the device at a desired target.

The invention may also include the additional step of reducing orstabilizing the temperature of lung tissue near to a treatment site.This may be accomplished for example, by injecting a cold fluid intolung parenchyma or into the airway being treated, where the airway isproximal, distal, or circumferentially adjacent to the treatment site.The fluid may be sterile normal saline, or any other bin-compatiblefluid. The fluid may be injected into treatment regions within the lungwhile other regions of the lung normally ventilated by gas. Or, thefluid may be oxygenated to eliminate the need for alternate ventilationof the lung. Upon achieving the desired reduction or stabilization oftemperature the fluid may be removed from the lungs. In the case where agas is used to reduce temperature, the gas may be removed from the lungor allowed to be naturally exhaled. One benefit of reducing orstabilizing the temperature of the lung may be to prevent excessivedestruction of the tissue, or to prevent destruction of certain types oftissue such as the epithelium, or to reduce the systemic healing loadupon the patient's lung.

Also contemplated as within the scope of the invention is the additionalstep of providing therapy to further reduce the effects of reversibleobstructive pulmonary disease or which aids the healing process aftersuch treatment. Some examples of therapy include, drug therapy, exercisetherapy, and respiratory therapy. The invention further includesproviding education on reversible obstructive pulmonary diseasemanagement techniques to further reduce the effects of the disease. Forexample, such techniques may be instruction on lifestyle changes,self-monitoring techniques to assess the state of the disease, and/ormedication compliance education.

There may be occurrences where it is necessary to reverse the effects ofthe treatment described herein. Accordingly, the invention furtherincludes a method for reversing a treatment to reduce the ability of thelung to produce at least one symptom of reversible obstructive pulmonarydisease comprising the step of stimulating re-growth of smooth muscletissue. The re-stimulation of the muscle may be accomplished by the useof electro-stimulation, exercising of the muscle and/or drug therapy.

The invention further includes methods of evaluating individuals havingreversible obstructive pulmonary disease, or a symptom thereof, as acandidate for a procedure to reduce the ability of the individual's lungto produce at least one symptom of reversible obstructive pulmonarydisease. The method comprises the steps of assessing the pulmonarycondition of the individual, comparing the pulmonary condition to acorresponding pre-determined state, and evaluating the individual as acandidate based upon the comparison.

In assessing the pulmonary condition, the method may comprise the stepsof performing pulmonary function tests on the individual to obtain apulmonary function value which is compared to a predetermined value.Examples of pre-determined values are found above.

The method of evaluating may further include the step of determining howthe individual's tissue will react to treatment allowing the treatmentto be tailored to the expected tissue response.

The method of evaluating may further comprises the step of pulmonaryfunction testing using a gas, a mixture of gases, or a composition ofseveral mixtures of gases to ventilate the lung. The difference inproperties of the gases may aid in the pulmonary function testing. Forexample, comparison of one or more pulmonary function test values thatare obtained with the patient breathing gas mixtures of varyingdensities may help to diagnose lung function. Examples of such mixturesinclude air, at standard atmospheric conditions, and a mixture of heliumand oxygen. Additional examples of pulmonary testing include tests thatmeasure capability and evenness of ventilation given diffusion ofspecial gas mixtures. Other examples of gases used in the describedtests, include but are not limited to, nitrogen, carbon monoxide, carbondioxide, and a range of inert gases.

The invention may also comprise the step of stimulating the lung toproduce at least one artificially induced symptom of reversibleobstructive pulmonary disease. Stimulating the symptoms of the diseasein an individual allows the individual to be evaluated as the individualexperiences the symptoms thereby allowing appropriate adjustment of thetreatment.

The method of evaluating may also comprise the step of obtainingclinical information from the individual and accounting for the clinicalinformation for treatment.

The method may further comprise the selection of a patient for treatmentbased upon a classification of the subtype of the patient's disease. Forexample, in asthma there are a number of ways to classify the diseasestate. One such method is the assessment of the severity of the disease.An example of a classification scheme by severity is found in the NHLBIExpert Panel 2 Guidelines for the Diagnosis and Treatment of Asthma.Another selection method may include selecting a patient by the type oftrigger that induces the exacerbation. Such triggers may be classifiedfurther by comparing allergic versus non-allergic triggers. Forinstance, an exercise induced bronchospasm (EIB) is an example of anon-allergenic trigger. The allergic sub-type may be further classifiedaccording to specific triggers (e.g., dust mites, animal dander, etc.).Another classification of the allergic sub-type may be according tocharacteristic features of the immune system response such as levels ofIgE (a class of antibodies that function in allergic reactions, alsocalled immunoglobulin). Yet another classification of allergic sub-typesmay be according to the expression of genes controlling certaininterleukins (e.g., IL-4, IL-5, etc.) which have been shown to play akey role in certain types of asthma.

The invention further comprises methods to determine the completion ofthe procedure and the effectiveness of the reduction in the lung'sability to produce at least one symptom of reversible obstructivepulmonary disease. This variation of the invention comprises assessingthe pulmonary condition of the individual, comparing the pulmonarycondition to a corresponding predetermined state, and evaluating theeffectiveness of the procedure based on the comparison. The inventionmay also comprise the steps of performing pulmonary function tests onthe individual to obtain at least one pulmonary function value, treatingthe lung to at least reduce the ability of the lung to produce at leastone symptom of reversible obstructive pulmonary disease, performing apost-procedure pulmonary function tests on the individual to obtain atleast one post pulmonary function value and comparing the two values.

This variation of the invention comprises obtaining clinicalinformation, evaluating the clinical information with the results of thetest to determine the effectiveness of the procedure. Furthermore, thevariation may include stimulating the lung to produce a symptom ofreversible obstructive pulmonary disease, assessing the pulmonarycondition of the patient, then repeating the stimulation before thepost-procedure pulmonary therapy. These steps allow comparison of thelung function when it is experiencing symptoms of reversible obstructivepulmonary disease, before and after the treatment, thereby allowing foran assessment of the improved efficiency of the lung during an attack ofthe disease.

The medical practitioners performing the treatments described herein maywish to treat a limited number of sites in the lung to produceacceptable results in lessening the severity of asthmatic or reversibleobstructive pulmonary disease symptoms. For example, if a patientrequires an increasing amount of medication (e.g., sedatives oranesthesia) to remain under continued control for performance of theprocedure, then a medical practitioner may limit the procedure timerather than risk overmedicating the patient. As a result, rather thantreating the patient continuously to complete the procedure, thepractitioner may plan to break the procedure in two or more sessions.Subsequently, increasing the number of sessions poses additionalconsequences on the part of the patient in cost, the residual effects ofany medication, adverse effects of the non-therapeutic portion of theprocedure, etc.

Accordingly, the invention includes methods of treating airways in alung to decrease asthmatic symptoms. The methods include measuring aparameter of an airway at a plurality of locations in a lung,identifying at least one treatment site from at least one of theplurality of locations based on the parameter, and applying energy tothe treatment site to reduce the ability of the site to narrow.

Identification of the treatment sites may comprise comparing theparameter to known or studied parameters and selecting those sites thatmeet or exceed specific criteria. Alternatively, or in combination,identification of treatment sites may comprise selecting the sites withthe most significant parameters, or delivering a treatment specificallytailored to the parameters measured at each individual site. Forexample, if the parameter comprises measuring contractile force or theamount of contraction, then sites having the highest quantitativeparameters may be selected as treatment sites. In another variation, themedical practitioner may simply rank the parameters in a desired orderof value and treat those sites that are believed to provide the mostbenefit. For example, the medical practitioner may chose to treat thetop 10% of sites having the most contraction, smooth muscle tissue, orother parameters as described herein. It is also contemplated that thediametrical size of the airway or the length of the airway segment maybe correlated to the ability for that site to narrow. For example, whenmeasuring a narrowed airway diameter relative to its natural diameter,the percentage change for a large diameter airway may be different thana percentage change for a smaller airway. In such a case, the medicalpractitioner may measure the airway diameter at each site fordetermining the course of treatment. In other words, the practitionermay deliver treatment to specific sites that meet certain criteria(e.g., sites having a certain diameter). Alternatively, or incombination, the practitioner may delivery treatment specificallytailored to each individual site based on a characteristic of the site(e.g., its diameter). For example, when delivering energy, thepractitioner could deliver more energy to larger diameter airway, andless energy to smaller diameter airways (or vice versa).

In those cases where more than one treatment site is identified, themethod may include the act of treating the new treatment site.

The method may also include correlating the treatment sites to a map 90,as shown in FIG. 5, the map may provide a graphical representation of abronchial tree. As shown, the various bronchioles 92 decrease in sizeand have many branches 96 as they extend into the right and left bronchi94. Accordingly, an efficient treatment may require identification ofpotential treatment sites, treated sites, and other areas of thebronchial tree.

This mapping may be performed for a variety of reasons. For example,prior to treatment, the correlation may identify general areas fortreatment by the medical practitioner. Once the area is treated, the mapmay then be marked to indicate a completed treatment. The treatment planprovided by the map should allow the medical practitioner a guide sothat it is possible to treat less than all of the lungs. The treatmentplan or map also may assist in avoiding double treatment of a particulartreatment site. It is contemplated that the map 90 may be an actualchart, whether in tangible form or electronic form. Furthermore, the mapmay be incorporated into the treatment system 32 or the user interface116 as discussed above. It is also contemplated that the map may be athree dimensional computer model, wherein the position of completedtreatment sites are recorded by storing the spatial coordinates of thesesites as each treatment is completed. As subsequent treatments are made,the user may compare the current position of the catheter to the map,which will aid in determining which site to treat next.

The parameters to be measured in accordance with the methods describedherein may be any parameter that is an indicator of or associated withsymptoms of asthma. For example, the parameter may be a measure ofpulmonary function values (see above), a measure of the contractileforce at which the airway contracts, a thickness or amount of the airwaysmooth muscle at a particular location, eosinophil counts near or at theactual or potential treatment site, degree of airflow within the airway,degree of contraction of the airway during an asthma episode or afterstimulation of the airway, metabolic rate to assess the presence ofsmooth muscle, electrical impedance to assess the nature of the airwaytissue, and/or degree of wheezing at a particular location, etc. Otherparameters indicative of asthma or a lack of airflow due to asthmaticsymptoms are also intended to be within the scope of this disclosure.

Methods of the present invention include first stimulating the airwayand then subsequently measuring the parameter. The stimulation may beperformed electrically (such as by placing a device within the airwayand stimulating using the settings described above). Alternatively, orin combination, the stimulation may be artificially induced using anagent, such as methacholine. For example, as shown in FIG. 6A, a device150 may deliver the agent 152 into the airway 2.

Once the airway contracts, the contraction may be measured or assessed.Although not shown, the contraction may be measured or assessed withoutmaking contact with the airway wall (e.g., visually with a retical; oroptically, via a camera). Alternatively, or in combination, as shown inFIG. 6B, a contraction measurement device 154 may be placed against theairway (either prior or during contraction) and expanded to measure anatural state of the airway. The contraction measurement device 154 thentransmits information regarding the contraction of the airway using, forexample, strain gauges 156 placed on moveable arms of the device. Thecontraction measurement device 154 may also deliver an agent to causecontraction of the airways. In this manner, the device 154 will be inplace while the airway contracts.

FIG. 6C illustrates another variation where a balloon catheter 158measures contraction of the airway. As the airway constricts, theballoon 160 increases in pressure. The pressure may then becharacterized to determine the degree of contractile force of theairway. It should be noted that the balloon catheter 158 may alsoinclude fluid delivery ports to deliver an agent or have electrodes toinduce the contraction. Other examples of devices that may be used tomeasure contraction of the airways are devices that measure the airwaydiameter mechanically or optically.

In another variation as shown in FIG. 6D, a device 162 (e.g., anultrasound balloon catheter, a non-balloon ultrasound catheter, acatheter (balloon or non-balloon) that is equipped to measure impedance,etc.), may be expanded within the airway to measure the thickness of theadjacent airway smooth muscle 14. Alternatively, as described above, themeasurement of the airway smooth muscle 14 may be achieved using theexternal imaging equipment 36 described above.

Another method of measuring parameters of an airway for identifyingtreatment sites comprises measuring eosinophil counts at the location.Eosinophils are white blood cells active in allergic diseases, parasiticinfections, and other disorders. It is believed that cosinophilscorrelate to the amount of inflammation in an airway. FIG. 6E shows oneway of obtaining an cosinophils count at a location in the lung. Asshown, a device 164 advances a needle 166 within the airway to collectthe eosinophils. Next, standard techniques are employed to measure theparticular eosinophil count at the site.

FIG. 6F illustrates another variation of the invention where a device168 measures airflow airflow at a location or near to a location fortreatment. The device 168 may be a hot-wire amenometer, where theairflow causes the heated wire 170 to cool and the rate of cooling ofthe wire provides information regarding the airflow.

In additional variations of the method, the medical practitioner maydeliver hyperpolarized helium or a radioactive isotope to aid in theimaging of the airways. External imaging, as shown FIGS. 4A and 4C maybe used to assess ventilation in the lung and select the areas thatconstrict as treatment sites.

Alternatively, the external imaging may take a first image of theairways. Next, an agent is applied (either locally, systemically, orlimited to a particular lobe) to induce contraction of the airways. Themedical practitioner may then obtain a second image of the airways forcomparison with the first to determine contraction of the airways.

In another variation of the invention, the parameter comprises assessinga metabolic rate at the location. If the measurement of the metabolicrate indicates the presence of a significant amount of smooth muscletissue, then the area may be designated as a treatment site. Themetabolic rate may be measured over a treatment site or over an area ofthe airways (e.g., a particular lobe or a section thereof.) Themeasurement of the metabolic rate may be performed using standardmeasuring techniques. For example, the device may deliver cool air tothe treatment site and then measure the rate at which the tissuetemperature returns to the original baseline temperature, therebyproviding a measurement of the calories used to bring the tissue back tothe baseline temperature. This would, in turn, provide a measure of theresponsiveness of the smooth muscle tissue because more reactive orresponsive tissue may correlate to a higher metabolic rate.

FIG. 7 illustrates one example of an energy transfer element 208. Inthis example the energy transfer element 208 is a “basket-type”configuration that requires actuation for expansion of the basket indiameter. Such a feature is useful when the device is operatedintralumenally or in anatomy such as the lungs due to the varying sizeof the bronchial passageways that may require treatment. As illustrated,the basket contains a number of arms 220 which carry electrodes (notshown). In this variation the arms 220 are attached to the elongatedshaft 204 at a proximal end while the distal end of the arms 220 areaffixed to a distal tip 222. To actuate the basket 208 a wire or tether224 is affixed to the distal tip 222 to enable compression of the arms220 between the distal tip 222 and elongate sheath 204.

FIG. 7 also illustrates the device 100 as being advanced through aworking channel 232 of a bronchoscope 318. While a bronchoscope 318 mayassist in the procedure, the device 100 may be used through directinsertion or other insertion means as well.

As noted above, some variations of the devices described herein havesufficient lengths to reach remote parts of the body (e.g., bronchialpassageways around 3 mm in diameter). FIG. 8 illustrates a configurationthat reduces the force required to actuate the device's basket or otherenergy transfer element.

FIG. 8 illustrates a cross section taken from the sheath 202 andelongate shaft 204. As shown, the sheath 202 includes an outer layer 226and an inner lubricious layer 228. The outer layer 226 may be anycommonly known polymer such as Nylon, PTFE, etc. The lubricious layers228 discussed herein may comprise a lubricious polymer (for example,HDPE, hydrogel, polytetrafluoroethylene). Typically, lubricious layer228 will be selected for optimal pairing with the shaft 204. One meansto select a pairing of polymers is to maximize the difference in Gibbssurface energy between the two contact layers. Such polymers may also bechosen to give the lubricious layer 228 a different modulus ofelasticity than the outer layer 226. For example, the modulus of thelubricious layer 228 may be higher or lower than that of the outer layer226.

Alternatively, or in combination, the lubricious layers may comprise afluid or liquid (e.g., silicone, petroleum based oils, food based oils,saline, etc.) that is either coated or sprayed on the interface of theshaft 204 and sheath 202. The coating may be applied at the time ofmanufacture or at time of use. Moreover, the lubricious layers 228 mayeven include polymers that are treated such that the surface propertiesof the polymer changes while the bulk properties of the polymer areunaffected (e.g., via a process of plasma surface modification onpolymer, fluoropolymer, and other materials). Another feature of thetreatment is to treat the surfaces of the devices with substances thatprovide antibacterial/antimicrobial properties.

In one variation of the invention, the shaft 204 and/or sheath 202 willbe selected from a material to provide sufficient column strength toadvance the expandable energy transfer element within the anatomy.Furthermore, the materials and or design of the shaft/sheath will permita flexibility that allows the energy transfer element to essentiallyself-align or self-center when expanded to contact the surface of thebody passageway. For example, when advanced through tortuous anatomy,the flexibility of this variation should be sufficient that when theenergy transfer element expands, the shaft and/or sheath deforms topermit self-centering of the energy transfer element. It is noted thatthe other material selection and/or designs described herein shall aidin providing this feature of the invention.

FIG. 8 also depicts a variation of a shaft 204 for use in the presentdevice. In this variation the shaft 204 includes a corrugated surface230. It is envisioned that the corrugated surface 230 may includeribbed, textured, scalloped, striated, undercut, polygonal, or anysimilar geometry resulting in a reduced area of surface contact with anyadjoining surface(s). The corrugated surface 230 may extend over aportion or the entire length of the shaft 204. In addition, the shape ofthe corrugations may change at varying points along the shaft 204.

The shaft 204 may also include one or more lumens 232, 234. Typically,one lumen will suffice to provide power to the energy transfer elements(as discussed below). However, in the variation shown, the shaft mayalso benefit from additional lumens (such as lumens 234) to supportadditional features of the device (e.g., temperature sensing elements,other sensor elements such as pressure or fluid sensors, utilizingdifferent lumens for different sensor leads, and fluid delivery orsuctioning, etc.). In addition the lumens may be used to deliver fluidsor suction fluid to assist in managing the moisture within thepassageway. Such management may optimize the electrical coupling of theelectrode to the tissue (by, for example, altering impedance). Since thedevice is suited for use in tortuous anatomy, a variation of the shaft204 may have lumens 234 that are symmetrically formed about an axis ofthe shaft. As shown, the additional lumens 234 are symmetric about theshaft 204. This construction provides the shaft 204 with a crosssectional symmetry that aid in preventing the shaft 204 from beingpredisposed to flex or bend in any one particular direction.

The invention herein is described by examples and a desired way ofpracticing the invention is described. However, the invention as claimedherein is not limited to that specific description in any manner.Equivalence to the description as hereinafter claimed is considered tobe within the scope of protection of this patent.

1-40. (canceled)
 41. A method of treating a lung, the method comprising:inserting a medical device into an airway of the lung, the medicaldevice including a catheter and a balloon disposed at a distal end ofthe catheter, wherein a distalmost portion of the catheter extendsdistally of a distalmost portion of the balloon; stimulating an airwayin the lung by introducing, via a port of the catheter, apharmacological agent into the airway to constrict the airway; afterstimulating the airway, measuring a constriction of the airway via theballoon; delivering a fluid to the airway to electrically couple anelectrode to tissue surrounding the airway; applying energy to thetissue, via the electrode and the fluid, to damage nerves disposedradially outward of the airway to reduce the ability of the lung toconstrict in response to a stimulus; conveying the fluid from theairway; and after applying energy, determining an effectiveness ofapplying energy by determining whether the lung has a reduced ability toproduce at least one symptom of reversible obstructive pulmonarydisease.
 42. The method of claim 41, wherein delivering the fluid to theairway and applying energy to the tissue occur only if the measuredconstriction is greater than a threshold value.
 43. The method of claim41, further including monitoring electrical impedance of the tissue. 44.The method of claim 41, wherein applying energy to the tissue includesapplying RF energy to the tissue.
 45. A method of treating a lung, themethod comprising: inserting a medical device into an airway of thelung, the medical device including a catheter and a balloon disposed ata distal end of the catheter, wherein a distalmost portion of thecatheter extends distally of a distalmost portion of the balloon;stimulating an airway in the lung; after stimulating the airway,measuring a parameter of the airway via the balloon; and applying energyto the tissue to damage nerves disposed radially outward of the airwayto reduce the ability of the lung to constrict in response to astimulus.
 46. The method of claim 45, further including delivering afluid to the airway to electrically couple an electrode to tissuesurrounding the airway.
 47. The method of claim 46, wherein applyingenergy to the tissue occurs through the electrode and the fluid.
 48. Themethod of claim 46, further including conveying the fluid from theairway.
 49. The method of claim 45, wherein applying energy only occursif the measured parameter is greater than a threshold value.
 50. Themethod of claim 49, wherein the measured parameter is a contraction ofthe airway.
 51. The method of claim 45, wherein, after applying energy,the method further includes determining an effectiveness of applyingenergy by determining whether the lung has a reduced ability to produceat least one symptom of reversible obstructive pulmonary disease. 52.The method of claim 45, wherein stimulating the airway includesintroducing a pharmacological agent into the airway.
 53. A method oftreating a lung, the method comprising: stimulating an airway in thelung to constrict the airway; after stimulating the airway, measuring aparameter of the airway via the balloon; delivering a fluid to theairway to electrically couple an electrode to tissue surrounding theairway; and applying energy to the tissue, via the electrode and thefluid, to damage nerves disposed radially outward of the airway toreduce the ability of the lung to constrict in response to a stimulus.54. The method of claim 53, further including conveying the fluid fromthe airway.
 55. The method of claim 53, further including, beforestimulating the airway, inserting a medical device into the airway, themedical device including a catheter and a balloon disposed at a distalend of the catheter, wherein a distalmost portion of the catheterextends distally of a distalmost portion of the balloon, and wherein themedical device provides the stimulation.
 56. The method of claim 55,wherein stimulating the airway includes introducing, via a port of thecatheter, a pharmacological agent into the airway.
 57. The method ofclaim 55, wherein delivering the fluid and applying energy to the tissueoccur only if the measured parameter is greater than a threshold value.58. The method of claim 57, wherein the measured parameter is acontractile force of the airway, and wherein the balloon measures thecontractile force.
 59. The method of claim 53, further including afterapplying energy, determining an effectiveness of applying energy bydetermining whether the lung has a reduced ability to produce at leastone symptom of reversible obstructive pulmonary disease.